FGFR2 residence in primary cilia is necessary for epithelial cell signaling
Primary cilium projects from cells to provide a communication platform with neighboring cells and the surrounding environment. This is ensured by the selective entry of membrane receptors and signaling molecules, producing fine-tuned and effective responses to the extracellular cues. In this study, we focused on one family of signaling molecules, the fibroblast growth factor receptors (FGFRs), their residence within cilia, and its role in FGFR signaling. We show that FGFR1 and FGFR2, but not FGFR3 and FGFR4, localize to primary cilia of the developing mouse tissues and in vitro cells. For FGFR2, we demonstrate that the ciliary residence is necessary for its signaling and expression of target morphogenic genes. We also show that the pathogenic FGFR2 variants have minimal cilium presence, which can be rescued for the p.P253R variant associated with the Apert syndrome by using the RLY-4008 kinase inhibitor. Finally, we determine the molecular regulators of FGFR2 trafficking to cilia, including IFT144, BBS1, and the conserved T429V430 motif within FGFR2.
Authors
- Michaela Kunova Bosakova (ORCID: https://orcid.org/0000-0002-7627-0344)
- Iva Gudernová
- Eliska Cizkova
- Adolf Koudelka (ORCID: https://orcid.org/0000-0002-9998-8383)
- Tomáš Gregor (ORCID: https://orcid.org/0000-0002-7974-1316)
- Bohumil Fafílek (ORCID: https://orcid.org/0000-0002-3869-7937)
- Gustavo Rico-Llanos (ORCID: https://orcid.org/0000-0001-5991-848X)
- Pavel Krejčı́ (ORCID: https://orcid.org/0000-0003-0618-9134)
- Zuzana Feketová (ORCID: https://orcid.org/0000-0003-4620-4634)
- Sara P. Abraham (ORCID: https://orcid.org/0000-0002-3754-9385)
- Katerina Svozilova
- Alexandru Niţă (ORCID: https://orcid.org/0000-0001-7681-0091)
- Lukáš Trantı́rek (ORCID: https://orcid.org/0000-0001-5948-4837)
- Tomáš Bárta (ORCID: https://orcid.org/0000-0003-0703-066X)
- Canan Celiker (ORCID: https://orcid.org/0000-0002-8216-2761)
- Aleksandra Czyrek (ORCID: https://orcid.org/0000-0002-8518-7075)
- Vlad-Constantin Ursachi (ORCID: https://orcid.org/0000-0002-8062-3595)
- Eman Ryad Elrefaay (ORCID: https://orcid.org/0000-0002-0993-7970)
- A Wiedłocha
- Pooja Dudeja (ORCID: https://orcid.org/0009-0000-1564-2354)
Institutions
- Oslo University Hospital (NO)
- University of Oslo (NO)
- Masaryk University (CZ)
- Central European Institute of Technology – Masaryk University (CZ)
- Czech Academy of Sciences, Institute of Animal Physiology and Genetics (CZ)
- St. Anne's University Hospital Brno (CZ)
- Institute of Animal Physiology of the Slovak Academy of Sciences (SK)
Publication Details
- Journal
- The Journal of Cell Biology
- Published
- 2025-04-21
- DOI
- https://doi.org/10.1083/jcb.202311030
- Citations
- 3
- Primary Topic
- Genetic and Kidney Cyst Diseases
- Type
- article
- Field-Weighted Citation Impact
- 5.45
Funders
- European Commission
- Ministerstvo Školství, Mládeže a Tělovýchovy
- Grantová Agentura České Republiky
- Masarykova Univerzita